A developmental sex difference in hippocampal neurogenesis is mediated by endogenous oestradiol

New born male and female rat pups were injected with the mitotic marker 5-bromo-2-deoxyuridine (BrdU) and oestradiol or agents that antagonize oestradiol action. The effects on cell number, proliferation, differentiation and survival were assessed at several time points. Significant differences between groups were determined by two- or thee-Way ANOVA.Newborn males had higher rates of cell proliferation than females. Oestradiol treatment increased cell proliferation in neonatal females, but not males, and in the CA1 region many of these cells differentiated into neurons. The increased rate of proliferation induced by neonatal oestradiol persisted until at least 3 weeks of age, suggesting an organizational effect. Administering the aromatase inhibitor, formestane, or the oestrogen receptor antagonist, tamoxifen, significantly decreased the number of new cells in males but not females.Endogenous oestradiol increased the rate of cell proliferation observed in newborn males compared to females. This sex difference in neonatal neurogenesis may have implications for adult differences in learning strategy, stress responsivity or vulnerability to damage or disease.Sex differences in the brain are widespread but of variable magnitude. Differences in the size of specific structures or subnuclei are well characterized, as are sex differences in the density and number of excitatory and inhibitory synapses within particular brain regions. Many sex differences in the brain are induced during a perinatal sensitive period by oestradiol following its central aromatization from testicularly derived androgen precursors (for review see [1]). The most robust neuroanatomical sex differences are found in the brain areas directly involved in reproduction, such as the preoptic area, hypothalamus and spinal cord [2-6]. The impact of steroids on these brain regions across the life-span is codified in the Organizational/Activational Hypothesis of sexual differentiation first postulated over 50